Spheronization has been described as a relatively complex technique in U.S. Pat. No. 5,049,394. This technology, also referred to as marumerization, which means "round maker" was initially described by N. Nakahara (Hicks, D. C. and Freese, H. L., "Extrusion and Spheronizing Equipment, Pharmaceutical Pelletization Technology, ed. I. Ghebre-Sellassie, Marcel Dekker, Inc. New York, N.Y., 1989, fn. 1, J. W. Conine and H. R. Hadley, "Preparation of small solid spheres for pharmaceutical use, in updated manuscript, Elanco Products Division, Eli Lilly and Company, Indianapolis, Ind.) The technology affords a process for the combination of drugs and excipients whereby the material to be spheronized is wet granulated and extruded through a screen to produce cylindrical strands of granulation. These strands are then placed on a spheronizer, which is a device which contains a rotating disc. As the strands hit the rotating disc, they tend to fragment. As the strands shorten, they begin to form spheres which are collected and dried.
Other spheronization technology such as high-shear granulation, pan granulation, centrifugal granulation, and rotary fluid-bed granulation has also been employed in the pharmaceutical industry. Each of these techniques have relied on the properties of the microcrystalline celluloses such as AVICEL (.TM.) to impart the proper plasticity to the material.
Spheronization is complicated by the fact that the granulation must maintain its plasticity during processing or the process will not work. That is, in the spheronization process, the granulation must maintain its malleability and cylindrical form after the extrusion process. Microcrystalline cellulose of various-grades is normally added to the granulation to assure the proper degree of plasticity. Generally, the blend must contain at least 15 to 20% of microcrystalline cellulose in order to remain in a form that is amenable to this process (Gamlen, M. J., Manuf. Chem., June, 1985, p 55 and see also O'Connor, R. E., and Schwartz, J. B., Drug Dev. Ind. Pharm. II, 1837, 1985). However, U.S. Pat. No. 5,049,394 has reported the use of as little as 10% microcrystalline cellulose when an aqueous ethanol solution was used to prepare the granulation.
Often, particularly when the spheronized beads are to be used in certain controlled release dosage forms and processes for medicaments that are incompatible with microcrystalline cellulose, it is necessary to avoid the use of microcrystalline cellulose. Further, it may be advantageous to incorporate inorganic salts, buffers, surfactants or osmotically active agents into the spheres which help to control the localized environment within the spheres in which the medicament will be initially solubilized or otherwise exposed to the fluid in the environment of use.
Surprisingly, it has been found that charged resins may be used in place of microcrystalline cellulose, to impart the desired plasticity for extrusion/spheronization. The procedure results in highly spherical multiparticulates which may be used directly or film coated to produce pharmaceutically useful drug delivery products.